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Nucleic Acids Research, 1991, Vol. 19, No. 7 1413-1419
© 1991


MOLECULAR BIOLOGY

Hypersensitive site 4 of the human ß globin locus control region

Sara Pruzina, Olivia Hanscombe, David Whyatt, Frank Grosveld* and Sjaak Philipsen

National Institute for Medical Research The Ridgeway, Mill Hill, London NW7 1AA, UK

* To whom correspondence should be addressed

Received January 28, 1991. Revised March 5, 1991. Accepted March 5, 1991.

The Locus Control Region (LCR) of the human ß globin gene domain is defined by four erythrold-specific DNasel hypersensitive sites (HSS) located upstream of this multigene cluster. The LCR confers copy number dependent high levels of erythrold specific expression to a linked transgene, independent of the site of integration. To assess the role of the individual hypersensitive sites of the LCR, we have localized HSS4 to a 280bp fragment that is functional both in murine erythroleukaemia (MEL) cells and in transgenic mice. This fragment coincides with the major area of hypersensitivity ‘in vivo’ and contains a number of DNasel footprints. Bandshift analysis shows that these footprints correspond to binding sites for the erythroid specific proteins GATA1 and NF-E2 and a number of ubiquitous proteins, including jun/fos, Sp1 and TEF2.


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